ACOLTREMON: 55 Adverse Event Reports & Safety Profile

TRYPTYR (acoltremon ophthalmic solution) 0.003% contains an agonist of TRPM8 ion channels. Acoltremon’s chemical name is (1 R ,2 S ,5 R )-2-isopropyl- N -(4-methoxyphenyl)-5-methylcyclohexane-1-carboxamide. The molecular formula of acoltremon is C 18 H 27 NO 2 and has a molecular weight of 289.42 g/mol. Acoltremon is a white to pale yellow crystalline solid, that is insoluble in water. TRYPTYR is a sterile, clear to slightly opalescent, colorless, isotonic aqueous solution for topical ophthalmic use, with a pH of approximately 7 and an osmolality of 280 to 330 mOsm/kg. Each mL of TRYPTYR contains active: acoltremon 0.003%; and inactives: polyoxyl 35 castor oil, sodium dihydrogen phosphate dihydrate, sodium chloride, hypromellose and purified water. Additionally, sodium hydroxide is used to adjust pH. TRYPTYR does not contain an anti-microbial preservative.

AND USAGE TRYPTYR is indicated for the treatment of the signs and symptoms of dry eye disease. TRYPTYR is a TRPM8 thermoreceptor agonist indicated for the treatment of the signs and symptoms of dry eye disease. ( 1 )

AND ADMINISTRATION Instill one drop in each eye twice daily (approximately 12 hours apart). ( 2 )

2.1 Recommended Dosage Instill one drop in each eye twice daily (approximately 12 hours apart).

2.2 Administration Instructions Wash hands before use. The single-dose vials are to be used immediately after opening and can be used to dose both eyes. Discard the single-dose vial, including any remaining contents, immediately after use. TRYPTYR can be used concomitantly with other topical ophthalmic eye drops. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart . Contact lenses should be removed prior to the administration of TRYPTYR and may be reinserted 15 minutes following administration. If one dose is missed, treatment should continue with the next dose.

None. None. ( 4 )

REACTIONS The most common adverse reaction was instillation site pain (50%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Alcon Laboratories, Inc. at 1-800-757-9780, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In patients with dry eye disease, 766 patients received at least one dose of TRYPTYR in four randomized controlled clinical trials across 71 sites in the United States. The most common ocular adverse reaction observed in controlled clinical studies with TRYPTYR was instillation site pain (50%). Less than 1% of patients discontinued therapy due to burning or stinging sensation in the eyes.

AND PRECAUTIONS To avoid the potential for eye injury and contamination, do not touch the vial tip to the eye or other surfaces. ( 5.1 )

5.1 Potential for Eye Injury and Contamination To avoid the potential for eye injury and contamination, do not touch the vial tip to the eye or other surfaces.

5.2 Use with Contact Lenses TRYPTYR should not be administered while wearing contact lenses. If contact lenses are worn, they should be removed prior to administration of the solution. Lenses may be reinserted 15 minutes following administration of TRYPTYR.